21-32515045-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_058187.5(EVA1C):​c.1181G>T​(p.Cys394Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,614,194 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C394Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00068 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 36 hom. )

Consequence

EVA1C
NM_058187.5 missense

Scores

18

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.913

Publications

3 publications found
Variant links:
Genes affected
EVA1C (HGNC:13239): (eva-1 homolog C) Enables heparin binding activity. Colocalizes with extracellular region. [provided by Alliance of Genome Resources, Apr 2022]
CFAP298-TCP10L (HGNC:54636): (CFAP298-TCP10L readthrough) This locus represents naturally occurring readthrough transcription between the neighboring chromosome 21 open reading frame 59 (C21orf59) and TCP10L (t-complex 10 like) genes on chromosome 21. Readthrough transcripts may encode a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Apr 2017]
TCP10L (HGNC:11657): (t-complex 10 like) Enables several functions, including identical protein binding activity; protein self-association; and transcription corepressor activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0033723414).
BP6
Variant 21-32515045-G-T is Benign according to our data. Variant chr21-32515045-G-T is described in ClinVar as [Benign]. Clinvar id is 742166.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000683 (104/152326) while in subpopulation SAS AF = 0.0207 (100/4830). AF 95% confidence interval is 0.0174. There are 2 homozygotes in GnomAd4. There are 80 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EVA1CNM_058187.5 linkc.1181G>T p.Cys394Phe missense_variant Exon 8 of 8 ENST00000300255.7 NP_478067.2 P58658-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EVA1CENST00000300255.7 linkc.1181G>T p.Cys394Phe missense_variant Exon 8 of 8 1 NM_058187.5 ENSP00000300255.2 P58658-1

Frequencies

GnomAD3 genomes
AF:
0.000683
AC:
104
AN:
152208
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00274
AC:
687
AN:
251104
AF XY:
0.00359
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000123
Gnomad OTH exome
AF:
0.00327
GnomAD4 exome
AF:
0.00129
AC:
1881
AN:
1461868
Hom.:
36
Cov.:
32
AF XY:
0.00187
AC XY:
1362
AN XY:
727238
show subpopulations
African (AFR)
AF:
0.0000896
AC:
3
AN:
33478
American (AMR)
AF:
0.0000224
AC:
1
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.0000504
AC:
2
AN:
39700
South Asian (SAS)
AF:
0.0199
AC:
1715
AN:
86254
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
0.000520
AC:
3
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000612
AC:
68
AN:
1112002
Other (OTH)
AF:
0.00147
AC:
89
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.473
Heterozygous variant carriers
0
94
188
283
377
471
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000683
AC:
104
AN:
152326
Hom.:
2
Cov.:
32
AF XY:
0.00107
AC XY:
80
AN XY:
74492
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41570
American (AMR)
AF:
0.0000654
AC:
1
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5188
South Asian (SAS)
AF:
0.0207
AC:
100
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68032
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
5
10
15
20
25
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000250
Hom.:
2
Bravo
AF:
0.000166
ExAC
AF:
0.00303
AC:
368
Asia WGS
AF:
0.00982
AC:
34
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jun 01, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
5.2
DANN
Benign
0.79
DEOGEN2
Benign
0.0085
T;T;.
Eigen
Benign
-0.94
Eigen_PC
Benign
-0.91
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.58
T;T;T
MetaRNN
Benign
0.0034
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L;.;.
PhyloP100
0.91
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.70
N;N;N
REVEL
Benign
0.012
Sift
Benign
0.65
T;T;T
Sift4G
Benign
0.69
T;T;T
Polyphen
0.0020
B;.;.
Vest4
0.13
MutPred
0.25
Gain of phosphorylation at S391 (P = 0.1364);.;.;
MVP
0.10
MPC
0.45
ClinPred
0.0010
T
GERP RS
1.5
Varity_R
0.077
gMVP
0.11
Mutation Taster
=99/1
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs145086534; hg19: chr21-33887355; API